The stereochemistry of the metabolism o the antiepileptics, phenytoin (DPH) and mephenytoin, will be studied in man. The optical configuration of the minor metabolite of phenytoin, 5-(m-hydroxyphenyl)-5-phenylhydantoin (m-HPPH) in urine will be determined by methods not involving isolation. Methods of analytical determination of m-HPPH applicable to large numbers of urine samples will be devised, making possible an investigation of the relation of unusual patterns of metabolism of DPH to hypersensitivity reactions. The metabolites of mephenytoin, 5-ethyl-5-phenylhydantoin (EPH) and 5-ethyl-5-(p-hydroxyphenyl) hydantoin (EHPH) will be isolated from urine by methods that do not change the proportions of the optical isomers, and these proportions will be determined by measurement of optical rotation. The absolute configurations of the optical isomers of m-HPPH, EPH, EHPH will be determined by single crystal X-ray diffraction methods, and the configuratons of the optically active metabolites will be related.